The objective of this research program is to understand the role of the gastrointestinal tract in producing satiety. The experiments examine the gastrointestinal consequences of food intake as possible inhibitory signals for feeding--signals which limit meal size and regulate the length of the intermeal interval: (1) The first aim is to identify the gut sites which produce satiety signals. This will be accomplished by a systematic exposure of single gut areas to food. Intake will be measured in the gastric fistula rat preparation. (2) The second aim is to identify the specific signals from the gut--humoral, neural, or both--which mediate satiety. We have already shown that injection of the duodenal hormone cholecystokinin (CCK) or its synthetic C-terminal octapeptide (SQ 19,844) decreases test meal size in rats. Using a sensitive bioassay specific for CCK, we plan to measure the plasma concentration of endogenous CCK during a meal to determine if the concentration of exogenous CCK required for a significant decrease of meal size is within the physiological range. We will also test feeding after exposure to other gut hormones, singly and in combination. We will examine feeding after a variety of gut nerve excisions. (3) The third aim is to identify the sites of action of identified gut satiety signals in the brain. This will be accomplished in the rat with the techniques of electrical stimulation, electrical lesioning, surgical disconnection, and intracerebral injection of hormones. We intend to undertake a similar series of experiments in the Rhesus monkey.